O02.5 A Phase II, Dose Ranging Study to Evaluate the Efficacy and Safety of Single-Dose Oral Solithromycin (CEM-101) For Treatment of Patients with Uncomplicated Urogenital Gonorrhoea

Objectives Emerging resistance to available treatment creates an urgent need for new therapies for uncomplicated gonorrhoea. Solithromycin, a new 4th generation macrolide with 3 ribosomal targets, is highly active against most antibiotic-resistant strains of Neisseria gonorrhoeae . A Phase II, dose ranging study to evaluate the efficacy and safety of single-dose oral solithromycin for uncomplicated urogenital gonorrhoea was conducted. Methods Consenting participants with suspected Neisseria gonorrhoeae infection were cultured at the urethra/cervix, rectum, and pharynx at enrollment and Day 7 . The primary outcome was bacterial eradication (conversion from positive baseline N. gonorrhoeae urethral/cervical culture to negative) at Day 7. Secondary outcomes included eradication of rectal or pharyngeal gonorrhoea and the eradication of gonococcal and chlamydial nucleic acids. Initially, eligible patients received a single 1200 mg oral dose of solithromycin; following demonstration of bacteriologic efficacy, a second cohort was treated with a single 1000 mg dose. Results Of 41 (19 M, 22 F) participants enrolled, 28 were treated with a 1200 mg dose and, to date, 13 with 1000 mg. Gonococcal eradication rates in 22 evaluable 1200 mg patients were 100% (22/22) for urethral/cervical, pharyngeal (5/5), and rectal (2/2) infections. Of 9 evaluable 1000 mg patients enrolled to date, gonococcal eradication rates have been 100% (9/9) for urethral/cervical, pharyngeal (2/2), and rectal (1/1) infections. Susceptibility data from 25 isolates show the median MIC (range) for solithromycin was 0.06 µg/mL (0.015–0.125) and for azithromycin was 0.125 µg/mL (0.06–0.5). Solithromycin was generally well-tolerated with mild dose-related gastrointestinal AEs (68%; 28/41). The most common AE was mild diarrhoea, occurring in 61% (17/28) of patients receiving the 1200 mg dose and 15% (2/13) of patients receiving the 1000 mg dose. Conclusions A single dose of 1200 or 1000 mg solithromycin appears to be well-tolerated and effective in eradicating N. gonorrhoeae.